Project Summary/Abstract The current opioid epidemic is one of the most important public health issues in the United States resulting in increased related disease, disability, and deaths. At least two million people in the nation have an opioid use disorder (OUD). Although medications are available as part of the treatment paradigm for OUD, adherence with treatment programs remains a problem. Emergent is developing an extended-release microparticle formulation of nalmefene (AP007) for the potential treatment of OUD. Nalmefene is an opioid receptor antagonist that was previously approved for treatment of opioid overdose-induced respiratory depression. In contrast to other opioid antagonists, nalmefene has a longer duration of action. AP007 is a unique formulation comprising of nalmefene-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles. When injected intramuscularly, AP007 is designed to act as a ?drug depot? with the purpose of continually releasing an effective dose of nalmefene and thus reduce cravings for opioids in patients with OUD. Reduction of cravings can help people who have already stopped using opioids remain drug-free. Emergent is currently developing AP007 and will have a lead formulation selected based on in vitro release kinetics data and in vivo pharmacokinetics data in rats by the start of the project. The objectives of the proposed project are to: (1) determine safety and efficacy of AP007 in a swine opioid use/withdrawal model, preliminary safety in a first- in-human Phase 1 study (UG3 Project Phase), and preliminary efficacy in a Phase 2a multidose study; and (2) further develop the efficacy and safety data for AP007 in human subjects in Phase 2 studies, and (3) initiate a Phase 3 pivotal efficacy clinical study (UH3 Project Phase). The proposed efficacy studies will compare efficacy of AP007 with Vivitrol, a monthly injection of naltrexone currently approved for treatment of OUD. Throughout the project, Emergent will leverage its experience developing therapeutics to meet with the FDA and align the development approach with FDA guidance. Depending on the results of this project, Emergent intends to complete the Phase 3 study and submit the results in a New Drug Application package to support potential licensure of AP007 as a long-acting therapeutic to help reduce opioid cravings because of addiction. Such a treatment is intended to increase adherence and reduce risk of relapse for patients with OUD. 1